Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Hypersensitivity
Hypersensitivity reactions may occur following administration of mesna for uroprotection.
Various cutaneous and subcutaneous reactions have been reported (see section 4.8).

There are also case reports of serious blistering and ulceration of the skin and mucous membranes. Some reactions were consistent with Stevens-Johnson syndrome.
The skin reactions were accompanied in some cases by one or several other symptoms, including fever, cardiovascular symptoms, signs of acute renal failure, lung symptoms, hematologic abnormalities, increased levels of liver enzymes, nausea, vomiting, pain in the extremities, arthralgia, myalgia, malaise, stomatitis and conjunctivitis (see section 4.8). Some reactions have presented as anaphylaxis. Fever accompanied by (for example) hypotension but no skin manifestations has also been reported.
Patients with an autoimmune disease are at increased risk of allergic or anaphylactoid reactions. Uromitexan 400 mg for uroprotection should therefore be given to such patients only after careful consideration of the risks and benefits and under medical monitoring.

Reactions to mesna ranging from serious to mild have been reported with the use of mesna to treat severe systemic autoimmune disorders and malignancies. In most cases, the reactions occurred during or after a first treatment occasion or several weeks after mesna exposure. In other cases, the initial reaction was not observed until several months after the exposure.
Symptoms tend to appear at shorter intervals following repeated exposure. The incidence and/or severity of reaction may vary with the dose administered. Some patients experienced reactions after re-exposure, which were of increasing severity in some cases.

Some patients with a history of a reaction showed positive delayed-type skin test results.
However, a negative delayed reaction does not exclude hypersensitivity to mesna. Positive immediate-type skin test reactions have occurred in patients regardless of previous mesna exposure or history of hypersensitivity reactions, and may be related to the concentration of the mesna solution used for testing.


Prescribers should
- be aware of reactions that may worsen with re-exposure and may in some cases become life-threatening
- be aware that hypersensitivity reactions to mesna might be interpreted as resembling the clinical picture of sepsis and, in patients with autoimmune disorders, as resembling an exacerbation of the underlying disease.

Thiol compounds
Mesna is a thiol compound (contains a sulfanyl-(SH-)group). Thiol compounds show some similarities in their adverse reaction profiles and may elicit severe skin reactions. Examples of drugs that are thiol compounds include amifostine, penicillamine and captopril.
It is not clear whether patients who experienced an adverse reaction to such a drug are at increased risk for reactions to another thiol compound. In these cases, special caution is required when using thiol compounds.

Mesna does not prevent hemorrhagic cystitis in all patients. Therefore, patients should be monitored accordingly.

Sufficient urinary output should be maintained, as with any oxazaphosphorine treatment.

Laboratory test interactions
Mesna treatment may cause false positive reactions in nitroprusside sodium-based urine tests (including dipstick tests) for ketone bodies. Adding glacial acetic acid can help to distinguish between false-positive results (fading cherry red color) and true-positive results (reddish purple, which becomes more intense).

Mesna treatment may cause false positive reactions in Tillman's reagent-based urine screening tests for ascorbic acid.

For other interactions with lab tests, see the pharmacokinetic data in section 5.2.

Pediatric use
Safety and effectiveness of mesna in pediatric patients (< 16 years) have not yet been established in clinical trials by Baxter, but the use of mesna in pediatric patients is described in the literature.

For use in pregnancy and lactation, see section 4.6.

Geriatric Use
In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. The ratio of oxazaphosphorines to mesna should remain unchanged.

Uromitexan 400 mg contains sodium, but less than 1 mmol (23 mg) sodium per 10 ml.

Effects on Driving

4.7   Effects on ability to drive and use machines

Patients undergoing treatment with mesna may experience side effects that would affect the ability to drive or use machines (including syncope, light-headedness, lethargy/drowsiness, dizziness and blurred vision).
Uromitexan 400 mg has major influence on the ability to drive and use machines.
It should be determined in each individual case whether the patient is fit to drive a vehicle or use machines.